A-395 是一种多梳抑制复合物 2 (PRC2) 蛋白质-蛋白质相互作用的拮抗剂，可有效抑制三聚体 PRC2 复合物 (EZH2-EED-SUZ12)，IC50为 18 nM。

A-395 is an antagonist of polycomb repressive complex 2 (PRC2) protein-protein interactions that potently inhibits the trimeric PRC2 complex (EZH2-EED-SUZ12, IC50: 18 nM).

The embryonic ectoderm development (EED) protein is an essential subunit of PRC2. A-395 antagonizes the H3K27me3 binding functions of EED. A-395 binds to EED in the H3K27me3-binding pocket, thereby preventing allosteric activation of the catalytic activity of PRC2. A-395 is capable of competing for H3K27me3 peptide binding to EED (IC50: 7 nM). A-395, but not the close chemical analog A-395N, modulates the activity of PRC2 in cells by potently reducing the H3K27 methyl mark in a highly selective manner. A-395 treatment inhibits both H3K27me2 and H3K27me3 (IC50s: 390 nM and 90 nM). Furthermore, A-395 treatment results in growth inhibition of human tumor cell lines sensitive to SAM-competitive EZH2 inhibitors.

1,000 multiple myeloma cells are seeded in each well of 96-well cell culture plates and treated with A-395 (0.001-100 μM) or DMSO control for 10 d before the cell proliferation assay. Cell proliferation assays are conducted with the CellTiter-Glo Luminescent Cell Viability Assay.

2089148-72-9

C26H35FN4O2S

486.65

DMSO:100 mg/mL (205.49 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years